Celecoxib‐induced bullous fixed drug eruption: An unusual presentation

Fixed drug eruption (FDE) is a drug reaction characterized by one or multiple erythematous lesions that recurs in a fixed site after taking the causative drug.1 It can be associated with blister formation defining the bullous FDE (BFDE). Celecoxib, cyclo‐oxygenase 2 selective inhibitor, is known to cause mild skin side effects2 although has never been implicated in inducing BFDE. We report herein a case of celecoxib‐induced BFDE confirmed by an oral provocation test.

A 34‐year‐old woman, with no relevant history, was prescribed celecoxib (Inibrex, capsules of 200 mg, Dar‐Essaydali) twice daily for the treatment of painful menstruation. One day later, she manifested an itching and burning sensation in the front face of the neck with a blistering eruption. Thus, she was referred to the Emergency Department. The physical examination revealed a bullous well‐circumscribed oval plaque measuring 8 cm of diameter located in the front face of the neck extending to the chin without mucosal involvement. Nikolsky's sign was negative. The patient had no fever, and systemic examination did not reveal any abnormality. Thus, celecoxib was discontinued, and the patient was prescribed topical steroids and antihistamines. Two days later, the cutaneous lesion resolved leaving a residual hyperpigmented patch. We note that, 2 years ago, the patient had developed similar lesion 5 days after celecoxib intake. A biopsy of the affected skin showed several apoptotic keratinocytes with a spongiosis in the epidermis associated with a marked vacuolization of the basal cell layer. These lesions were accompanied by a perivascular infiltrate of lymphocytes, eosinophils, and neutrophils. Six weeks after the resolution of the acute eruption, patch test to celecoxib (10% in petroleum) was applied on the residual pigmented lesion, showing a negative reaction at 48‐ and 72‐hour reading. The next day, an oral rechallenge test was started, with a prior consent of the patient. The provocation test consisted of the administration of a gradual dose of this drug at a dose of 50 mg weekly for 4 weeks. The first dose was followed, 4 hours later, by a flare up of the lesion without the onset of new ones (Figure 1). The acute reactivation faded spontaneously 4 days later.

Figure 1.

Positive reaction to celecoxib at 4 hours after the start of the oral provocation test

We describe an original case of celecoxib‐induced BFDE, where the accountability of the latter drug was found to be definite (score = 10) according the Naranjo causality scale in view of the temporal relationship between drug intake and BFDE onset, the remission of the acute eruption after celecoxib withdrawal, the previous history of FDE after celecoxib intake, the histopathological findings, and the positive rechallenge to this drug. To our knowledge, only three clinical observations of celecoxib‐induced FDE have been reported (PubMed database)2, 3 and three others with etoricoxib.1, 4 However, no one among these described patients exhibited with a bullous pattern. Therefore, we consider that our case is the first to describe a bullous variant of FDE induced by celecoxib and generally with cyclo‐oxygenase 2 selective inhibitors. In our case, the patch test to celecoxib, performed with the recommended concentration (10% in petrolatum),5 was negative. Patch tests are a useful device for investigation of delayed drug hypersensitivity such as FDE; however, its sensitivity and specificity in cases of celecoxib‐induced FDE is still unknown.6 Oral challenge tests started the first day at 1/10 of the therapeutic dose followed on the second day, if there is no reaction, by full therapeutic dose is a protocol usually used.7 In our case, we have used a protocol starting with a low dose of the suspected drug with a prolonged time, as the cutaneous lesion was a bullous variant. This test resulted in a positive reactivation following the first administered dose. Therefore, the provocation test seems to be the gold standard in the diagnosis of FDE induced by celecoxib, as suggested by the European Academy of Allergy and Clinical Immunology (EAACI) interest group on drug hypersensitivity.8 In this paper, we report the first case of celecoxib‐induced BFDE and underlines the usefulness of the oral provocation test in the determination of drug imputability. Clinicians should be aware of such serious side effect that could be induced by celecoxib.

COMPETING INTEREST

There are no competing interests to declare.